Understanding the role of natural killer (NK) cells in disease pathogenesis

Viral infections are implicated in a wide variety of diseases. Our lab is principally interested in identifying regulatory mechanisms that govern the immune response to infection, and understanding how these factors contribute to pathogen elimination, tissue damage, and resolution of inflammation. Our investigations usually originate in murine models of infection, wherein specific immune elements can be manipulated in an intact organism during acute or persistent infection. Where possible we attempt to translate the paradigms established in mice to human cells in culture. We specialize in a wide variety of techniques that measure immune function, including a number of flow cytometry-based analyses.

Our most recent work has uncovered a vital regulatory role for natural killer (NK) cells in the pathogenesis of diseases associated with virus infections in mice. This activity of NK cells prevented fatal pathology associated with some viral inoculums by favoring functional exhaustion of antiviral T cells. NK cell killing of activated CD4 T cells was identified as a major mechanism contributing to regulation of virus-specific CD8 T cell functionality in the context of persistent virus replication. We are currently assessing the precise antigenic nature of the cells targeted by NK cells during virus infection in order to determine pathways that could be exploited to limit or augment this regulatory activity in therapy of human diseases, including autoimmunity and chronic viral infections. Moreover, we are exploring whether and how the immunoregulatory activity of NK cells contributes to immune dysfunction in the elderly or to the efficacy of certain vaccine regimens.